Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible
Autor: | Tamir S Rashid, Marlies C Glatz, Samuel Ji Blackford, Gilbert O. Fruhwirth, Ewelina Kurtys, Candice Ashmore-Harris, Benjamin Grimsdell |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Sodium-iodide symporter Radionuclide imaging Cell Genetic Vectors Induced Pluripotent Stem Cells Biology Article Cell therapy 03 medical and health sciences 0302 clinical medicine In vivo Genes Reporter Transduction Genetic Human sodium iodide symporter medicine Humans Induced pluripotent stem cell lcsh:QH301-705.5 Reporter gene Lentivirus Cell Differentiation Cell Biology General Medicine Cell biology Transplantation Induced pluripotent stem cells 030104 developmental biology medicine.anatomical_structure surgical procedures operative Cell tracking lcsh:Biology (General) Hepatocyte Hepatocytes Genetic Engineering 030217 neurology & neurosurgery Hepatocyte-like cells Developmental Biology |
Zdroj: | Ashmore-Harris, C, Blackford, S JI, Grimsdell, B, Kurtys, E, Glatz, M, Rashid, T S & Fruhwirth, G O 2019, ' Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible ', Stem Cell Research, vol. 41, 101599 . https://doi.org/10.1016/j.scr.2019.101599 Stem Cell Research Stem Cell Research, Vol 41, Iss, Pp-(2019) |
Popis: | Highlights • iPSC-derived hepatocyte-like cells (HLCs) rendered traceable in vivo. • Reproducible lentivirus-based gene transfer during the differentiation process. • Protocol and reporter expression did not negatively impact on HLC maturation. • Proof-of-principle shown for whole-body SPECT/CT-afforded HLC in vivo tracking. Primary hepatocyte transplantation (HTx) is a safe cell therapy for patients with liver disease, but wider application is circumvented by poor cell engraftment due to limitations in hepatocyte quality and transplantation strategies. Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (hiPSC) are considered a promising alternative but also require optimisation of transplantation and are often transplanted prior to full maturation. Whole-body in vivo imaging would be highly beneficial to assess engraftment non-invasively and monitor the transplanted cells in the short and long-term. Here we report a lentiviral transduction approach designed to engineer hiPSC-derived HLCs during differentiation. This strategy resulted in the successful production of sodium iodide symporter (NIS)-expressing HLCs that were functionally characterised, transplanted into mice, and subsequently imaged using radionuclide tomography. Graphical abstract Image, graphical abstract |
Databáze: | OpenAIRE |
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